Besides the conventional treatment of cancer, which is based on surgical measures, the use of chemotherapy medicaments and/or irradiation, immunotherapy with antibodies has become established. Equally, a large number of biotechnological products which also include, inter alia, therapeutic antibodies, are already recognized as a therapy option for the treatment of autoimmune diseases. So-called HIV-neutralizing antibodies are currently being investigated for the treatment of AIDS in clinical studies.
The target structures, the so-called antigens, differ greatly for the various diseases and thus the mode of action of the respective antibody therapies can be very different depending on these target structures. Surface antigens which serve as target structure for the treatment of malignant diseases, include inter alia overexpressed, cancer-associated, membrane-bound proteins (EGFR/HER2/VEGFR) or also cell-specific proteins (CD20/CD52). The number of antigen-positive cells in the development of lymphomas is extremely large, with the result that a reduction in this cell population represents a recognized therapeutic aim. Besides the treatment of lymphomas the target-oriented depletion of antigen-positive cells is also suitable for the treatment of autoimmune diseases and optionally for the suppression of the immune response such as e.g. in the case of transplantation. Antibodies or also fusion proteins, directed against cellular messengers such as the soluble tumour necrosis factor, are important medicaments for the treatment of autoimmune diseases.
The first modern monoclonal antibodies (immunoglobulins mostly of the IgG1 type) were of murine origin, i.e. they were prepared by means of mouse or rat hybridoma cell lines. These IgG1 molecules are however recognized as foreign by the human body, with the result that they are neutralized by the human immune system. For this reason, more modern, so-called chimeric antibodies have been prepared, consisting of murine portions and human portions in the IgG structure. So-called “humanization”, up to the biotechnologically optimized variant of the completely human antibodies, represents the next step towards the further minimization of the murine portions. Chimeric, humanized and human IgG1 antibodies can be used over a longer period, for example over months, during therapy. (Abdullah N., Cancer Immunther. 48, 517-524), (Adams G P, Weiner L M, Nature Biotechnology, 2005; 23 (9): 1146-1157).
Moreover, immunotherapies are carried out inter alia with Fcγ receptor-binding agents. Fcγ receptors (FCRs) are a family of receptors which are specific to the Fc parts of immunoglobulin (IgG). These receptors have important tasks in the normal immune system and its resistance to infections. Thus IgGs are a class of molecules which bind the Fcγ receptor.
There are receptors for each immunoglobulin class. They are defined by the class of immunoglobulin to which they bind. For example the Fcγ receptor (FcγR) binds IgG, the Fcε receptor (FcεR) binds IgE etc. Among the FcγR receptors a distinction is made between three members of sub-families: FcγRI, which is a receptor with high affinity for IgG, FcγRIIs, which are receptors with low affinity for IgG, but which bind well to aggregates of immune complexes, and FcγRIIIs, which are receptors with low affinity which bind to immune complexes.
Although all these receptors are structurally related to each other, they have different tasks.